RNAi Screen Identifies Multiple Members of RRAS Signaling Cascade as Modulators of Mutant Htt Toxicity.

<p>(A) Results with siRNAs that target RRAS pathway proteins. Values are means and standard deviations observed in the primary screen and in the retest (caspase activity values are expressed as percent of non-targeting siRNA control). ND = not determined. Colored circles refer to Panel B. Additional results with relevant siRNAs are presented in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003042#pgen.1003042.s008" target="_blank">Table S2</a>. (B) Diagram showing the relationships of proteins that when inhibited in HEK293T cells (red) or ST<i>Hdh</i>^Q111/Q111 cells (blue) by siRNA, or in <i>Drosophila</i> by RNAi or loss-of-function (LOF) alleles (olive; see <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003042#pgen-1003042-g004" target="_blank">Figure 4</a> and <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003042#pgen.1003042.s005" target="_blank">Figure S5</a>) suppress mutant Htt toxicity. Gray lines indicate relationships from published observations that may not play a role in these HD cell models. References for the pathway interconnections are presented within the text and in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003042#pgen.1003042.s009" target="_blank">Text S1</a>. (C) Modifier effects of loss-of-function in Ras pathway components on motor impairment in <i>Drosophila</i> expressing mutant Htt. S = suppressor. Colored circles refer to Panel B.